{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:14:37Z","timestamp":1789647277742,"version":"4.0.0"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Integrins are cell surface adhesion molecules. They bridge the intracellular and extracellular environments, enabling bidirectional transmembrane signaling and regulating immune responses. However, it remains unclear whether integrin protein \u03b21 (ITG\u03b21) is involved in innate immune responses. In our previous study, we demonstrated that porcine epidemic diarrhea virus (PEDV) can induce type I interferon (IFN-I) production. In this study, we observed that ITG\u03b21 expression is rapidly induced following PEDV infection and further established that PEDV infection primarily promoted ITG\u03b21 expression through upregulation of the transcription factor c-Myc. We hypothesized that ITG\u03b21 might be involved in PEDV-induced innate immune responses through IFN-I production. Our investigation revealed ITG\u03b21 overexpression promotes the phosphorylation and subsequent nuclear translocation of both interferon regulatory factor 3 (IRF3) and NF-\u03baB, thereby enhancing SeV-induced IFN-\u03b2 promoter activity. Furthermore, we showed that ITG\u03b21 functions as an activator in the melanoma differentiation-associated protein 5 (MDA5)-mediated IFN-I signaling pathway. More importantly, we demonstrated that ITG\u03b21 is critically involved in PEDV-induced IFN-I antiviral responses. Mechanistically, ITG\u03b21 facilitates MDA5 oligomerization by specifically interacting with its caspase activation and recruitment domain (CARD), thereby enhancing dsRNA-recruitment capacity. In summary, the findings of this study indicate that ITG\u03b21 acts as an activator of the MDA5-dependent IFN-I antiviral innate immune response and positively regulates the MDA5-mediated RIG-I-like receptor signaling pathway.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Porcine epidemic diarrhea virus (PEDV), an alpha coronavirus, severely impacts newborn piglets, leading to acute manifestations including vomiting, diarrhea, dehydration, and high mortality rates in suckling piglets. These consequences have devastating implications for the global swine industry. Within the host\u2019s innate antiviral response, RIG-I-like receptors (RLRs) are critical for the activation of the interferon signaling pathway. Integrin proteins, known for their role in regulating bidirectional signal transduction across the cell membrane, are associated with numerous viral infections. In this study, utilizing PEDV as an infection model, we demonstrated that overexpression of ITG\u03b21 suppresses PEDV replication, while knockdown of ITG\u03b21 expression enhances it. Additionally, ITG\u03b21 significantly augments PEDV-induced type I interferon production in host cells. We further elucidated that ITG\u03b21 interacts with the 2CARD region of MDA5, promoting MDA5 oligomerization and the transmission of activation signals. These findings establish ITG\u03b21 as a positive regulatory factor in MDA5-mediated RLR signaling pathway. These findings not only identify ITG\u03b21 as a novel host antiviral protein against PEDV but also reveal, for the first time, a previously unrecognized function of ITG\u03b21 in the cellular innate antiviral immune response.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01553-25","type":"journal-article","created":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T13:06:51Z","timestamp":1760706411000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["The integrin protein ITG\u03b21 effectively suppresses porcine epidemic diarrhea virus replication through facilitating MDA5 oligomerization and subsequent activation of the type I interferon signaling 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